Twin studies have provided fundamental information about how genes and environment contribute to individual differences in brain structure and cognitive function in health and psychiatric disease and how these influences change during development. Previous twin studies in older children, adolescents and adults indicate that genetic and environmental influences are region/structure specific and change with age. Early childhood is period of rapid structural and functional brain development that is implicated in the pathogenesis of many psychiatric disorders. Therefore, there is a critical need to understand the role of genetic and environmental contributions to brain structure and function in this crucial period of development. The Early Brain Development in Twins study has been the first, and to our knowledge the only, twin study of early childhood brain development. To date we have enrolled and studied over 275 twin pairs, at birth, 1, 2, 4, and 6 years and provided novel and previously unknown information about genetic and environmental influences on brain development in early childhood. In the next funding cycle, we propose to complete our twin study of early childhood brain development by following the current cohort to age 6. MRIs, including structural, diffusion tensor, and resting state functional imaging, will be done at ages , 4, and 6 years. Cognitive development, including RDoC constructs of language and working memory will be assessed. Additional innovations for this funding cycle include the application of a recently developed methodology for delineating cortical thickness and surface area in very young children, and the addition of resting state fMRI. Knowledge gained in this study will improve our basic understanding of human brain development, allow us to determine how modifiable abnormal developmental trajectories associated with risk for psychiatric disease may be, and help us determine when in development early interventions would have the greatest impact. Relevance New knowledge gained in this study will provide a dramatically improved framework for understanding genetic and environmental influences on early childhood brain development, a period of risk for many neuropsychiatric disorders and will provide the fundamental information critical for developing preventative strategies for these disorders.